evidence-based practice for helping a couple to understand the reason for their pregnancy loss. To determine the etiology of such a loss, at present the test of choice is microarray analysis of products of conception or fetal tissue, which are available in most cases. We also strove to educate clinicians about the value of testing for exceedingly rare microdeletions in the general population and to highlight the important issues of informed consent and genetic counseling. We look forward to future studies on microdeletion testing, a very exciting research area. Until relevant data are published, we believe it is prudent to offer the test as an opt-in rather than an opt-out test. Financial Disclosure: Dr. O’Brien receives compensation from Sequenom for educational lectures she gives on noninvasive prenatal testing. The other author did not report any potential conflicts of interest.
Neeta L. Vora, MD Department of Obstetrics and Gynecology, University of North Carolina-Chapel Hill, Director of Reproductive Genetics, Director of the Maternal Serum Screening Laboratory, Chapel Hill, North Carolina Barbara M. O’Brien, MD Department of Obstetrics and Gynecology, Women and Infant’s Hospital, Rhode Island, Director, Perinatal Genetics, Co-Director, Prenatal Diagnosis Center, Director, Maternal Fetal Medicine Fellowship, Providence, Rhode Island
REFERENCES 1. Vora NL, O’Brien BM. Noninvasive prenatal testing for microdeletion syndromes and expanded trisomies: proceed with caution. Obstet Gynecol 2014;123:1097–99. 2. Jensen TJ, Dzakula Z, Deciu C, van den Boom D, Ehrich M. Detection of microdeletion 22q11.2 in a fetus by next-generation sequencing of maternal plasma. Clin Chem 2012;58:1148–51.
a timely and pertinent review of the pregnancy complicated by fetal growth restriction. However, I believe their general recommendation to perform followup fetal biometric assessment at 2-week intervals might not be appropriate for most patients and will increase the risk of a false-positive ultrasound result, causing unnecessary interventions. The current American College of Obstetricians and Gynecologists Practice Bulletin states, “the optimal interval for fetal growth assessment and the optimal surveillance regimen has not been established. Most growthrestricted fetuses can be adequately evaluated with serial ultrasonography every 3–4 weeks.”2 A fascinating study by Mongelli et al used established ultrasound growth data and mathematical modeling to suggest that the risk of a falsepositive result is directly related to the time interval between ultrasound growth assessments. They found the shorter the interval, the greater the risk of a false-positive finding. For example, at 32 weeks of gestation, the risk of a false-positive result was 16.9% if the ultrasound biometric assessment interval was only 2 weeks. But the false-positive rate decreased to just 3.2% if the interval was 4 weeks.3 Perhaps if the fetal Doppler assessment is markedly abnormal, it might be a reasonable compromise to perform follow-up fetal growth (biometric) assessment at 2 weeks, because the fetus is at greater risk of deterioration and harm. However, in the fetus with normal amniotic fluid and Doppler assessment, interval fetal growth assessment should be performed at 3-week or 4-week intervals to reduce the risk of unnecessary intervention. Financial Disclosure: The author did not report any potential conflicts of interest.
Dana P. Damron, MD Billings, Montana
REFERENCES
A Practical Approach to Fetal Growth Restriction To the Editor: I read with great interest the excellent article by Copel and Bahtiyar.1 This was
380
Letters to the Editor
1. Copel JA, Bahtiyar MO. A practical approach to fetal growth restriction. Obstet Gynecol 2014;123:1057–69. 2. Fetal growth restriction. Practice Bulletin No. 134. American College of Obstetricians and Gynecologists. Obstet Gynecol 2013;121:1122–33.
3. Mongelli M, Ek S, Tambyrajia R. Screening for fetal growth restriction: a mathematical model of the effect of time interval and ultrasound error. Obstet Gynecol 1998;92:908–12.
In Reply: We appreciate the kind words of Dr. Damron regarding our Clinical Expert Series article on fetal growth restriction1 and his bringing to our attention the work of Mongelli et al.2 Mongelli et al’s article was a theoretical extrapolation from a large Danish population of lowrisk women and suggested a high false-positive rate of diagnosis of fetal growth restriction based on lack of abdominal circumference growth if ultrasonography is performed at 2week intervals. The false-positive rate of any study depends on the prevalence of disease in the population, and a lowrisk Danish cohort is not the same as any group of women preselected to have fetal growth issues. In other words, the results of this mathematical model are not applicable to the realworld situation of when to repeat scans in women with small fetuses. That study also used failure to detect true abdominal circumference growth as the outcome rather than actual fetal growth, so it did not use a standard definition of fetal growth restriction. The American College of Obstetricians and Gynecologists’ Practice Bulletin no. 134 states, “Most growth-restricted fetuses can be adequately evaluated with serial ultrasonography every 3–4 weeks; ultrasound assessment of growth should not be performed more frequently than every 2 weeks because the inherent error associated with ultrasonographic measurements can preclude an accurate assessment of interval growth.”3 In the high-risk population we see, 2-week intervals for growth scans remains our preference because of the potential for major morbidity occurring with longer interscan intervals. We typically see patients who are at risk of growth restriction, such as those with hypertension, at monthly intervals to avoid falsepositive diagnoses. Financial Disclosure: The authors did not report any potential conflicts of interest.
OBSTETRICS & GYNECOLOGY
Neeta L. Vora, MD Department of Obstetrics and Gynecology, University of North Carolina-Chapel Hill, Director of Reproductive Genetics, Director of the Maternal Serum Screening Laboratory, Chapel Hill, North Carolina Barbara M. O’Brien, MD Department of Obstetrics and Gynecology, Women and Infant’s Hospital, Rhode Island, Director, Perinatal Genetics, Co-Director, Prenatal Diagnosis Center, Director, Maternal Fetal Medicine Fellowship, Providence, Rhode Island
REFERENCES 1. Vora NL, O’Brien BM. Noninvasive prenatal testing for microdeletion syndromes and expanded trisomies: proceed with caution. Obstet Gynecol 2014;123:1097–99. 2. Jensen TJ, Dzakula Z, Deciu C, van den Boom D, Ehrich M. Detection of microdeletion 22q11.2 in a fetus by next-generation sequencing of maternal plasma. Clin Chem 2012;58:1148–51.
a timely and pertinent review of the pregnancy complicated by fetal growth restriction. However, I believe their general recommendation to perform followup fetal biometric assessment at 2-week intervals might not be appropriate for most patients and will increase the risk of a false-positive ultrasound result, causing unnecessary interventions. The current American College of Obstetricians and Gynecologists Practice Bulletin states, “the optimal interval for fetal growth assessment and the optimal surveillance regimen has not been established. Most growthrestricted fetuses can be adequately evaluated with serial ultrasonography every 3–4 weeks.”2 A fascinating study by Mongelli et al used established ultrasound growth data and mathematical modeling to suggest that the risk of a falsepositive result is directly related to the time interval between ultrasound growth assessments. They found the shorter the interval, the greater the risk of a false-positive finding. For example, at 32 weeks of gestation, the risk of a false-positive result was 16.9% if the ultrasound biometric assessment interval was only 2 weeks. But the false-positive rate decreased to just 3.2% if the interval was 4 weeks.3 Perhaps if the fetal Doppler assessment is markedly abnormal, it might be a reasonable compromise to perform follow-up fetal growth (biometric) assessment at 2 weeks, because the fetus is at greater risk of deterioration and harm. However, in the fetus with normal amniotic fluid and Doppler assessment, interval fetal growth assessment should be performed at 3-week or 4-week intervals to reduce the risk of unnecessary intervention. Financial Disclosure: The author did not report any potential conflicts of interest.
Dana P. Damron, MD Billings, Montana
REFERENCES
A Practical Approach to Fetal Growth Restriction To the Editor: I read with great interest the excellent article by Copel and Bahtiyar.1 This was
380
Letters to the Editor
1. Copel JA, Bahtiyar MO. A practical approach to fetal growth restriction. Obstet Gynecol 2014;123:1057–69. 2. Fetal growth restriction. Practice Bulletin No. 134. American College of Obstetricians and Gynecologists. Obstet Gynecol 2013;121:1122–33.
3. Mongelli M, Ek S, Tambyrajia R. Screening for fetal growth restriction: a mathematical model of the effect of time interval and ultrasound error. Obstet Gynecol 1998;92:908–12.
In Reply: We appreciate the kind words of Dr. Damron regarding our Clinical Expert Series article on fetal growth restriction1 and his bringing to our attention the work of Mongelli et al.2 Mongelli et al’s article was a theoretical extrapolation from a large Danish population of lowrisk women and suggested a high false-positive rate of diagnosis of fetal growth restriction based on lack of abdominal circumference growth if ultrasonography is performed at 2week intervals. The false-positive rate of any study depends on the prevalence of disease in the population, and a lowrisk Danish cohort is not the same as any group of women preselected to have fetal growth issues. In other words, the results of this mathematical model are not applicable to the realworld situation of when to repeat scans in women with small fetuses. That study also used failure to detect true abdominal circumference growth as the outcome rather than actual fetal growth, so it did not use a standard definition of fetal growth restriction. The American College of Obstetricians and Gynecologists’ Practice Bulletin no. 134 states, “Most growth-restricted fetuses can be adequately evaluated with serial ultrasonography every 3–4 weeks; ultrasound assessment of growth should not be performed more frequently than every 2 weeks because the inherent error associated with ultrasonographic measurements can preclude an accurate assessment of interval growth.”3 In the high-risk population we see, 2-week intervals for growth scans remains our preference because of the potential for major morbidity occurring with longer interscan intervals. We typically see patients who are at risk of growth restriction, such as those with hypertension, at monthly intervals to avoid falsepositive diagnoses. Financial Disclosure: The authors did not report any potential conflicts of interest.
OBSTETRICS & GYNECOLOGY
